Table 6.

Ortho-fluoro and ortho-methyl (3-chloro-4,5-dialkoxybenzamido)benzoic acids.

				Potency and Selectivity				PK
Compd	R1O	R2O	R3	RARα rel EC50a	β/α ratio b	γ/α ratiob	LogDpH 7.4d	intrinsic Clinte		rat pof
								mouse	human	AUC	Cl	F%
53	iPrO	MeO	F	6.7	609	17,600	1.0	11	0.3	10,871	15	15
54	iPrO	EtO	F	1.1	487	6169	1.4	17.9	3.3	15,376	12	12
43	iPrO	iPrO	F	2.7	34	300	2.0	18.8	6.9	–	–	–
55	iPrO	MeO	Me	4.7c	241	509	1.3	10.6	1.5	–	–	–
44	iPrO	iPrO	Me	0.97	45	2947	2.3	26.2	15	77,670	5.4	66
56	iPrO	EtO	Me	1.6	200	11,000	1.8	37.6	5.3	70,765	7	40
57	EtO	iPrO	Me	7	286	1675	1.9	25.7	8.7	–	–	–
58	MeO	EtO	Me	33	210	>250	–	18.4	–	–	–	–
59		EtO	Me	2.6	58	38,461	–	42.3	–	–	–	–
45	tBuO	tBuO	Me	0.64	13,200	128	2.9	36.2	28.7	–	–	–

^aRelative EC₅₀.

^bRelative EC₅₀ ratios and ^cpartial agonist see Table 1.

^dMeasured by octanol/buffer shake flask method at pH 7.4 see Table 2.

^eCl_int (µL/min/mg protein) and ^fAUC (ng·min mL⁻¹), Cl (mL min⁻¹ kg⁻¹) see Table 2.